RESUMO
OBJECTIVES: To perform a comparative analysis of the extended APPROPRIATE trial of measures of reactive nitrogen species and antioxidant capacity in patients having resistant hypertension with controlled hypertension and healthy controls. RESULTS: Mean serum NO2- and NOx levels were significantly lower and mean AOC was significantly higher in patients with controlled hypertension (n = 38) and healthy controls (n = 38) compared to resistant hypertension (RHTN) patients (n = 40) at the pre-intervention stage (p < 0.001). The serum NO2-, NOx and AOC levels of both controlled hypertension and healthy controls were comparable to those of the RHTN patients following treatment with propranolol (n = 18). Considering all samples (n = 114) we noted that there were significant weak and moderate positive correlations between NO2- levels with systolic blood pressure (SBP) and diastolic blood pressure (DBP) (r = 0.396, p < 0.001 and r = 0.292, p = 0.004) as well as total NOx levels with SBP and DBP (r = 0.636 and r = 0.480 respectively, p < 0.001). Conversely, there was a significant negative correlation between AOC levels with SBP and DBP (r= -0.846 and r = -0.626 respectively, p < 0.001).
Assuntos
Anti-Hipertensivos , Antioxidantes , Hipertensão , Propranolol , Espécies Reativas de Nitrogênio , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/sangue , Hipertensão/fisiopatologia , Feminino , Masculino , Pessoa de Meia-Idade , Antioxidantes/metabolismo , Propranolol/uso terapêutico , Propranolol/farmacologia , Anti-Hipertensivos/uso terapêutico , Estudos de Casos e Controles , Espécies Reativas de Nitrogênio/sangue , Espécies Reativas de Nitrogênio/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Adulto , Seguimentos , IdosoRESUMO
Reduction-oxidation (redox) chemistry plays a vital role in human homeostasis. These reactions play critical roles in energy generation, as part of innate immunity, and in the generation of secondary messengers with various functions such as cell cycle progression or the release of neurotransmitters. Despite this cornerstone role, if left unchecked, the body can overproduce reactive oxygen species (ROS) or reactive nitrogen species (RNS). When these overwhelm endogenous antioxidant systems, oxidative stress (OS) occurs. In neonates, OS has been associated with retinopathy of prematurity (ROP), leukomalacia, and bronchopulmonary dysplasia (BPD). Given its broad spectrum of effects, research has started to examine whether OS plays a role in necrotizing enterocolitis (NEC). In this paper, we will discuss the basics of redox chemistry and how the human body keeps these in check. We will then discuss what happens when these go awry, focusing mostly on NEC in neonates.
Assuntos
Enterocolite Necrosante , Oxirredução , Estresse Oxidativo , Espécies Reativas de Nitrogênio , Espécies Reativas de Oxigênio , Humanos , Enterocolite Necrosante/metabolismo , Enterocolite Necrosante/patologia , Espécies Reativas de Oxigênio/metabolismo , Recém-Nascido , Espécies Reativas de Nitrogênio/metabolismo , Antioxidantes/metabolismo , AnimaisRESUMO
Reactive oxygen and nitrogen species are small reactive molecules derived from elements in the airâoxygen and nitrogen. They are produced in biological systems to mediate fundamental aspects of cellular signaling but must be very tightly balanced to prevent indiscriminate damage to biological molecules. Small molecule probes can transmute the specific nature of each reactive oxygen and nitrogen species into an observable luminescent signal (or even an acoustic wave) to offer sensitive and selective imaging in living cells and whole animals. This review focuses specifically on small molecule probes for superoxide, hydrogen peroxide, hypochlorite, nitric oxide, and peroxynitrite that provide a luminescent or photoacoustic signal. Important background information on general photophysical phenomena, common probe designs, mechanisms, and imaging modalities will be provided, and then, probes for each analyte will be thoroughly evaluated. A discussion of the successes of the field will be presented, followed by recommendations for improvement and a future outlook of emerging trends. Our objectives are to provide an informative, useful, and thorough field guide to small molecule probes for reactive oxygen and nitrogen species as well as important context to compare the ecosystem of chemistries and molecular scaffolds that has manifested within the field.
Assuntos
Espécies Reativas de Nitrogênio , Espécies Reativas de Oxigênio , Espécies Reativas de Nitrogênio/metabolismo , Espécies Reativas de Nitrogênio/química , Espécies Reativas de Oxigênio/metabolismo , Animais , Humanos , Sondas Moleculares/química , Sondas Moleculares/metabolismo , Ácido Peroxinitroso/química , Ácido Peroxinitroso/metabolismoRESUMO
Invasion and adhesion of neutrophils into tissues and their concomitant secretion play an important role in the development of vascular pathologies, including abdominal aortic aneurysm (AAA). Chronic administration of angiotensin II is used to initiate AAA formation in mice. The role of aldosterone in this process is being studied. We conducted for the first time a complex comparative study of the effects of angiotensin II and aldosterone on the adhesion of human neutrophils to fibronectin and the concomitant secretion of proteins, free amino acids as well as reactive oxygen (ROS) and nitrogen (NO) species. Neither angiotensin II nor aldosterone affected the attachment of neutrophils to fibronectin and the concomitant production of ROS. We showed for the first time that aldosterone stimulated the release of amino acid hydroxylysine, a product of lysyl hydroxylase, the activity of which is positively correlated with cell invasiveness. Aldosterone also initiates the secretion of matrix metalloproteinase 9 (MMP-9) and cathepsin G, which may reorganize the extracellular matrix and stimulate the recruitment and adhesion of neutrophils to the aortic walls. Angiotensin II did not affect protein secretion. It may contribute to neutrophil-induced vascular injury by inhibiting the production of NO or by increasing the secretion of isoleucine. Our results suggest that it is aldosterone-induced neutrophil secretion that may play a significant role in neutrophil-induced vascular wall destruction in angiotensin II-induced AAA or other vascular complications.
Assuntos
Aldosterona , Angiotensina II , Adesão Celular , Neutrófilos , Espécies Reativas de Oxigênio , Humanos , Angiotensina II/metabolismo , Angiotensina II/farmacologia , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Neutrófilos/metabolismo , Aldosterona/metabolismo , Adesão Celular/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Fibronectinas/metabolismo , Células Cultivadas , Catepsina G/metabolismo , Aminoácidos/metabolismo , Espécies Reativas de Nitrogênio/metabolismo , Aneurisma da Aorta Abdominal/metabolismo , Aneurisma da Aorta Abdominal/patologiaRESUMO
Cold atmospheric plasma (CAP) has emerged as an innovative tool with broad medical applications, including ovarian cancer (OC) treatment. By bringing CAP in close proximity to liquids such as water or cell culture media, solutions containing reactive oxygen species (ROS) and reactive nitrogen species (RNS) are generated, called plasma-activated media (PAM). In this systematic review, we conduct an in-depth analysis of studies focusing on PAM interactions with biological substrates. We elucidate the diverse mechanisms involved in the activation of different media and the complex network of chemical reactions underlying the generation and consumption of the prominent reactive species. Furthermore, we highlight the promises of PAM in advancing biomedical applications, such as its stability for extended periods under appropriate storage conditions. We also examine the application of PAM as an anti-cancer and anti-metastatic treatment for OC, with a particular emphasis on its ability to induce apoptosis via distinct signaling pathways, inhibit cell growth, suppress cell motility, and enhance the therapeutic effects of chemotherapy. Finally, the future outlook of PAM therapy in biomedical applications is speculated, with emphasis on the safety issues relevant to clinical translation.
Assuntos
Neoplasias Ovarianas , Gases em Plasma , Espécies Reativas de Nitrogênio , Espécies Reativas de Oxigênio , Humanos , Neoplasias Ovarianas/tratamento farmacológico , Feminino , Gases em Plasma/farmacologia , Gases em Plasma/uso terapêutico , Espécies Reativas de Nitrogênio/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Meios de Cultura , Movimento Celular/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêuticoRESUMO
Exogenous electrical stimulation has attracted considerable attention due to the advantages of microelectric induction and subsequent biological effects such as actin reorganization and reactive oxygen species (ROS) generation. Herein, an injectable hydrogel of BPR-ARG@Gel (BAG) with pyroelectric BPR nanoparticle loading and l-arginine (ARG) introduction was fabricated for advanced cancer therapy in vivo. Due to the photothermal effect, the holes and electrons in BPR nanoparticles were separated to produce an open-circuit voltage and consequently catalyze water H2O to generate toxic superoxide (â¢O2-) and hydroxyl radicals (â¢OH). These ROS substances further oxidize ARG to produce NO for synergistic tumor treatments. The mice experiments indicated that the employment of BAG hydrogel incorporation with a near-infrared laser downregulated the heat shock protein and recruited immune cells with 5-fold-enhanced expression of proinflammatory cytokines of interferon-γ. It was also noteworthy that the injectable hydrogel of BAG substantially induced the generation of reactive oxygen/nitrogen species (ROS/RNS) with reliable biosafety and strong tumor inhibition. Overall, these findings have provided potentially new inspirations and a feasible strategy to translate this multifunctional hydrogel toward tumor therapy in a pyroelectric stimulation manner.
Assuntos
Hidrogéis , Espécies Reativas de Oxigênio , Animais , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Hidrogéis/química , Hidrogéis/farmacologia , Catálise , Raios Infravermelhos , Humanos , Arginina/química , Espécies Reativas de Nitrogênio/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/terapia , Neoplasias/patologia , Linhagem Celular Tumoral , Nanopartículas/química , Camundongos Endogâmicos BALB C , Antineoplásicos/química , Antineoplásicos/farmacologiaRESUMO
Soil salinity is a major constraint for sustainable agricultural productivity, which together with the incessant climate change may be transformed into a severe threat to the global food security. It is, therefore, a serious concern that needs to be addressed expeditiously. The overproduction and accumulation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) are the key events occurring during salt stress, consequently employing nitro-oxidative stress and programmed cell death in plants. However, very sporadic studies have been performed concerning different aspects of nitro-oxidative stress in plants under salinity stress. The ability of plants to tolerate salinity is associated with their ability to maintain the cellular redox equilibrium mediated by both non-enzymatic and enzymatic antioxidant defense mechanisms. The present review emphasizes the mechanisms of ROS and RNS generation in plants, providing a detailed evaluation of how redox homeostasis is conserved through their effective removal. The uniqueness of this article stems from its incorporation of expression analyses of candidate genes for different antioxidant enzymes involved in ROS and RNS detoxification across various developmental stages and tissues of rice, utilizing publicly available microarray data. It underscores the utilization of modern biotechnological methods to improve salinity tolerance in crops, employing different antioxidants as markers. The review also explores how various transcription factors contribute to plants' ability to tolerate salinity by either activating or repressing the expression of stress-responsive genes. In summary, the review offers a thorough insight into the nitro-oxidative homeostasis strategy for extenuating salinity stress in plants.
Assuntos
Homeostase , Espécies Reativas de Nitrogênio , Espécies Reativas de Oxigênio , Tolerância ao Sal , Espécies Reativas de Oxigênio/metabolismo , Espécies Reativas de Nitrogênio/metabolismo , Tolerância ao Sal/genética , Regulação da Expressão Gênica de Plantas , Estresse Oxidativo , Antioxidantes/metabolismo , Oxirredução , Plantas/metabolismo , SalinidadeRESUMO
KEY MESSAGE: Plants respond to environmental challenges by producing reactive species such as ROS and RNS, which play critical roles in signaling pathways that lead to adaptation and survival strategies. Understanding these pathways, as well as their detection methods and effects on plant development and metabolism, provides insight into increasing crop tolerance to combined stresses. Plants encounter various environmental stresses (abiotic and biotic) that affect plant growth and development. Plants sense biotic and abiotic stresses by producing different molecules, including reactive species, that act as signaling molecules and stimulate secondary messengers and subsequent gene transcription. Reactive oxygen and nitrogen species (ROS and RNS) are produced in both physiological and pathological conditions in the plasma membranes, chloroplasts, mitochondria, and endoplasmic reticulum. Various techniques, including spectroscopy, chromatography, and fluorescence methods, are used to detect highly reactive, short-half-life ROS and RNS either directly or indirectly. In this review, we highlight the roles of ROS and RNS in seed germination, root development, senescence, mineral nutrition, and post-harvest control. In addition, we provide information on the specialized metabolism involved in plant growth and development. Secondary metabolites, including alkaloids, flavonoids, and terpenoids, are produced in low concentrations in plants for signaling and metabolism. Strategies for improving crop performance under combined drought and pathogen stress conditions are discussed in this review.
Assuntos
Plantas , Espécies Reativas de Nitrogênio , Espécies Reativas de Oxigênio , Transdução de Sinais , Estresse Fisiológico , Espécies Reativas de Oxigênio/metabolismo , Espécies Reativas de Nitrogênio/metabolismo , Plantas/metabolismo , Fenômenos Fisiológicos Vegetais , Desenvolvimento VegetalRESUMO
Malignant melanoma is the most lethal form of skin cancer. As a promising anti-cancer agent, plasma-activated water (PAW) rich in reactive oxygen and nitrogen species (RONS) has shown significant potential for melanoma treatment. However, rapid decay of RONS and inefficient delivery of PAW in conventional injection methods limit its practical applications. To address this issue, here we report a new approach for the production of plasma-activated cryo-microneedles (PA-CMNs) patches using custom-designed plasma devices and processes. Our innovation is to incorporate PAW into the PA-CMNs that are fabricated using a fast cryogenic micro-molding method. It is demonstrated that PA-CMNs can be easily inserted into skin to release RONS and slow the decay of RONS thereby prolonging their bioactivity and effectiveness. The new insights into the effective melanoma treatment suggest that the rich mixture of RONS within PA-CMNs prepared by custom-developed hybrid plasma-assisted configuration induces both ferroptosis and apoptosis to selectively kill tumor cells. A significant inhibition of subcutaneous A375 melanoma growth was observed in PA-CMNs-treated tumor-bearing nude mice without any signs of systemic toxicity. The new approach based on PA-CMNs may potentially open new avenues for a broader range of disease treatments.
Assuntos
Melanoma , Espécies Reativas de Nitrogênio , Espécies Reativas de Oxigênio , Neoplasias Cutâneas , Animais , Melanoma/terapia , Melanoma/patologia , Melanoma/metabolismo , Melanoma/tratamento farmacológico , Humanos , Camundongos , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapia , Neoplasias Cutâneas/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Linhagem Celular Tumoral , Espécies Reativas de Nitrogênio/metabolismo , Gases em Plasma/uso terapêutico , Apoptose , Agulhas , Ensaios Antitumorais Modelo de Xenoenxerto , Camundongos NusRESUMO
MAIN CONCLUSION: Reactive nitrogen species mitigate the deteriorative effect of accelerated seed ageing by affecting the glutathione concentration and activities of GR and GPX-like. The treatment of apple (Malus domestica Borkh.) embryos isolated from accelerated aged seeds with nitric oxide-derived compounds increases their vigour and is linked to the alleviation of the negative effect of excessive oxidation processes. Reduced form of glutathione (GSH) is involved in the maintenance of redox potential. Glutathione peroxidase-like (GPX-like) uses GSH and converts it to oxidised form (GSSG), while glutathione reductase (GR) reduces GSSG into GSH. The aim of this work was to investigate the impact of the short-time NOx treatment of embryos isolated from apple seeds subjected to accelerated ageing on glutathione-related parameters. Apple seeds were subjected to accelerated ageing for 7, 14 or 21 days. Isolated embryos were shortly treated with NOx and cultured for 48 h. During ageing, in the axes of apple embryos, GSH and GSSG levels as well as half-cell reduction potential remained stable, while GR and GPX-like activities decreased. However, the positive effect of NOx in the vigour preservation of embryos isolated from prolonged aged seeds is linked to the increased total glutathione pool, and above all, higher GSH content. Moreover, NOx increased the level of transcripts encoding GPX-like and stimulated enzymatic activity. The obtained results indicate that high seed vigour related to the mode of action of NO and its derivatives is closely linked to the maintenance of higher GSH levels.
Assuntos
Glutationa , Malus , Sementes , Malus/genética , Malus/metabolismo , Sementes/metabolismo , Sementes/genética , Glutationa/metabolismo , Espécies Reativas de Nitrogênio/metabolismo , Glutationa Redutase/metabolismo , Glutationa Redutase/genética , Glutationa Peroxidase/metabolismo , Glutationa Peroxidase/genética , Oxirredução , Óxido Nítrico/metabolismo , Regulação da Expressão Gênica de PlantasRESUMO
The Oryza genus, containing Oryza sativa L., is quintessential to sustain global food security. This genus has a lot of sophisticated molecular mechanisms to cope with environmental stress, particularly during vulnerable stages like flowering. Recent studies have found key involvements and genetic modifications that increase resilience to stress, including exogenous application of melatonin, allantoin, and trehalose as well as OsSAPK3 and OsAAI1 in the genetic realm. Due to climate change and anthropogenic reasons, there is a rise in sea level which raises a concern of salinity stress. It is tackled through osmotic adjustment and ion homeostasis, mediated by genes like P5CS, P5CR, GSH1, GSH2, and SPS, and ion transporters like NHX, NKT, and SKC, respectively. Oxidative damage is reduced by a complex action of antioxidants, scavenging RONS. A complex action of genes mediates cold stress with studies highlighting the roles of OsWRKY71, microRNA2871b, OsDOF1, and OsICE1. There is a need to research the mechanism of action of proteins like OsRbohA in ROS control and the action of regulatory genes in stress response. This is highly relevant due to the changing climate which will raise a lot of environmental changes that will adversely affect production and global food security if certain countermeasures are not taken. Overall, this study aims to unravel the molecular intricacies of ROS and RNS signaling networks in Oryza plants under stress conditions, with the ultimate goal of informing strategies for enhancing stress tolerance and crop performance in this important agricultural genus.
Assuntos
Regulação da Expressão Gênica de Plantas , Oryza , Espécies Reativas de Nitrogênio , Espécies Reativas de Oxigênio , Transdução de Sinais , Estresse Fisiológico , Oryza/genética , Oryza/metabolismo , Oryza/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Estresse Fisiológico/genética , Espécies Reativas de Nitrogênio/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genéticaRESUMO
Bitter taste receptors (TAS2Rs) are not only responsible for taste perception in the oral cavity, but are spread throughout the body, generating a widespread chemosensory system. In humans, 25 subtypes have been identified and are differentially expressed in tissues and organs, including in the immune system. In fact, several TAS2R subtypes have been detected in neutrophils, lymphocytes, B and T cells, NK cells, and monocytes/macrophages, in which they regulate various protective functions of the innate immune system. Given its recognized anti-inflammatory and antioxidant activity, and the generally protective role of bitter taste receptors, in this work, we studied TAS2R46's potential in the protection of human monocyte/macrophage DNA from stress-induced damage. Through both direct and indirect assays and a single-cell gel electrophoresis assay, we demonstrated that absinthin, a specific TAS2R46 agonist, counteracts the release of reactive oxygen species (ROS) and reactive nitrogen species (RNS) and reduces DNA damage in both cell types. Even though the release of ROS from monocytes/macrophages is fundamental for contrast pathogen agents, supraphysiological ROS production impairs their function, finally leading to cell death. Our results highlight TAS2R46 as a novel player involved in the protection of monocytes and macrophages from oxidative stress damage, while simultaneously supporting their antimicrobial activity.
Assuntos
Macrófagos , Monócitos , Estresse Oxidativo , Espécies Reativas de Oxigênio , Receptores Acoplados a Proteínas G , Humanos , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Monócitos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Macrófagos/metabolismo , Dano ao DNA , Espécies Reativas de Nitrogênio/metabolismoRESUMO
Inflammatory bowel disease (IBD) is a chronic immune-mediated condition that affects the digestive system and includes Crohn's disease (CD) and ulcerative colitis (UC). Although the exact etiology of IBD remains uncertain, dysfunctional immunoregulation of the gut is believed to be the main culprit. Amongst the immunoregulatory factors, reactive oxygen species (ROS) and reactive nitrogen species (RNS), components of the oxidative stress event, are produced at abnormally high levels in IBD. Their destructive effects may contribute to the disease's initiation and propagation, as they damage the gut lining and activate inflammatory signaling pathways, further exacerbating the inflammation. Oxidative stress markers, such as malondialdehyde (MDA), 8-hydroxy-2'-deoxyguanosine (8-OHdG), and serum-free thiols (R-SH), can be measured in the blood and stool of patients with IBD. These markers are elevated in patients with IBD, and their levels correlate with the severity of the disease. Thus, oxidative stress markers can be used not only in IBD diagnosis but also in monitoring the response to treatment. It can also be targeted in IBD treatment through the use of antioxidants, including vitamin C, vitamin E, glutathione, and N-acetylcysteine. In this review, we summarize the role of oxidative stress in the pathophysiology of IBD, its diagnostic targets, and the potential application of antioxidant therapies to manage and treat IBD.
Assuntos
Doenças Inflamatórias Intestinais , Estresse Oxidativo , Humanos , Estresse Oxidativo/fisiologia , Doenças Inflamatórias Intestinais/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Biomarcadores/metabolismo , Antioxidantes/metabolismo , Antioxidantes/uso terapêutico , Espécies Reativas de Nitrogênio/metabolismo , AnimaisRESUMO
Rapid drug clearance and off-target effects of therapeutic drugs can induce low bioavailability and systemic side effects and gravely restrict the therapeutic effects of inflammatory bowel diseases (IBDs). Here, we propose an amplifying targeting strategy based on orally administered gallium (Ga)-based liquid metal (LM) nano-agents to efficiently eliminate reactive oxygen and nitrogen species (RONS) and modulate the dysregulated microbiome for remission of IBDs. Taking advantage of the favorable adhesive activity and coordination ability of polyphenol structure, epigallocatechin gallate (EGCG) is applied to encapsulate LM to construct the formulations (LM-EGCG). After adhering to the inflamed tissue, EGCG not only eliminates RONS but also captures the dissociated Ga to form EGCG-Ga complexes for enhancive accumulation. The detained composites protect the intestinal barrier and modulate gut microbiota for restoring the disordered enteral microenvironment, thereby relieving IBDs. Unexpectedly, LM-EGCG markedly decreases the Escherichia_Shigella populations while augmenting the abundance of Akkermansia and Bifidobacterium, resulting in favorable therapeutic effects against the dextran sulfate sodium-induced colitis.
Assuntos
Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Animais , Doenças Inflamatórias Intestinais/tratamento farmacológico , Administração Oral , Microbioma Gastrointestinal/efeitos dos fármacos , Camundongos , Catequina/análogos & derivados , Catequina/química , Catequina/administração & dosagem , Catequina/farmacologia , Gálio/química , Gálio/farmacologia , Modelos Animais de Doenças , Inflamação/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Colite/tratamento farmacológico , Humanos , Espécies Reativas de Nitrogênio/metabolismoRESUMO
PURPOSE: We aimed to investigate early effects of exogenously administered adropin (AD) on neurological function, endothelial nitric oxide synthase (eNOS) expression, nitrite/nitrate levels, oxidative stress, and apoptosis in subarachnoid hemorrhage (SAH). METHODS: Following intracerebroventricular AD administration (10 µg/5 µl at a rate of 1 µl/min) SAH model was carried out in Sprague-Dawley rats by injection of autologous blood into the prechiasmatic cistern. The effects of AD were assessed 24 h following SAH. The modified Garcia score was employed to evaluate functional insufficiencies. Adropin and caspase-3 proteins were measured by ELISA, while nitrite/nitrate levels, total antioxidant capacity (TAC) and reactive oxygen/nitrogen species (ROS/RNS) were assayed by standard kits. eNOS expression and apoptotic neurons were detected by immunohistochemical analysis. RESULTS: The SAH group performed notably lower on the modified Garcia score compared to sham and SAH + AD groups. Adropin administration increased brain eNOS expression, nitrite/nitrate and AD levels compared to SHAM and SAH groups. SAH produced enhanced ROS/RNS generation and reduced antioxidant capacity in the brain. Adropin boosted brain TAC and diminished ROS/RNS production in SAH rats and no considerable change amongst SHAM and SAH + AD groups were detected. Apoptotic cells were notably increased in intensity and number after SAH and were reduced by AD administration. CONCLUSIONS: Adropin increases eNOS expression and reduces neurobehavioral deficits, oxidative stress, and apoptotic cell death in SAH model. Presented results indicate that AD provides protection in early brain injury associated with SAH.
Assuntos
Fármacos Neuroprotetores , Óxido Nítrico Sintase Tipo III , Estresse Oxidativo , Hemorragia Subaracnóidea , Animais , Masculino , Ratos , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Proteínas Sanguíneas , Encéfalo/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Modelos Animais de Doenças , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Neurônios/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/patologia , Fármacos Neuroprotetores/farmacologia , Nitratos/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Nitritos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Peptídeos/farmacologia , Ratos Sprague-Dawley , Espécies Reativas de Nitrogênio/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Hemorragia Subaracnóidea/metabolismo , Hemorragia Subaracnóidea/tratamento farmacológico , Hemorragia Subaracnóidea/patologiaRESUMO
Oxidative stress results from the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in quantities exceeding the potential activity of the body's antioxidant system and is one of the risk factors for the development of vascular dysfunction in diabetes and exposure to ionizing radiation. Being the secondary products of normal aerobic metabolism in living organisms, ROS and RNS act as signaling molecules that play an important role in the regulation of vital organism functions. Meanwhile, in high concentrations, these compounds are toxic and disrupt various metabolic pathways. The various stress factors (hyperglycemia, gamma-irradiation, etc.) trigger free oxygen and nitrogen radicals accumulation in cells that are capable to damage almost all cellular components including ion channels and transporters such as Na+/K+-ATPase, BKCa, and TRP channels. Vascular dysfunctions are governed by interaction of ROS and RNS. For example, the reaction of ROS with NO produces peroxynitrite (ONOO-), which not only oxidizes DNA, cellular proteins, and lipids, but also disrupts important signaling pathways that regulate the cation channel functions in the vascular endothelium. Further increasing in ROS levels and formation of ONOO- leads to reduced NO bioavailability and causes endothelial dysfunction. Thus, imbalance of ROS and RNS and their affect on membrane ion channels plays an important role in the pathogenesis of vascular dysfunction associated with various disorders.
Assuntos
Estresse Oxidativo , Espécies Reativas de Oxigênio , Humanos , Animais , Estresse Oxidativo/efeitos da radiação , Espécies Reativas de Oxigênio/metabolismo , Lesões por Radiação/metabolismo , Lesões por Radiação/fisiopatologia , Lesões por Radiação/etiologia , Estresse Nitrosativo/efeitos da radiação , Espécies Reativas de Nitrogênio/metabolismo , Transdução de Sinais , Angiopatias Diabéticas/metabolismo , Angiopatias Diabéticas/etiologia , Angiopatias Diabéticas/fisiopatologia , Diabetes Mellitus/metabolismo , Diabetes Mellitus/fisiopatologia , Radiação IonizanteRESUMO
As well known, surface discharge cold plasma has efficient inactivation ability and a variety of RONS are main active particles for inactivation, but their synergistic mechanism is still not clear. Therefore, surface discharge cold plasma system was applied to treat Pseudomonas fluorescens to study bacterial inactivation mechanism and energy benefit. Results showed that energy efficiency was directly proportional to applied voltage and inversely proportional to initial concentration. Cold plasma treatment for 20 min was inactivated by approximately > 4-log10Pseudomonas fluorescens and application of â¢OH and 1O2 scavengers significantly improved survival rate. In addition, â¢OH and 1O2 destroyed cell membrane structure and membrane permeability, which promoted diffusion of RONS into cells and affecting energy metabolism and antioxidant capacity, leading to bacterial inactivation. Furthermore, accumulation of intracellular NO and ONOOH was related to infiltration of exogenous RNS, while accumulation of â¢OH, H2O2, 1O2, O2- was the result of joint action of endogenous and exogenous ROS. Transcriptome analysis revealed that different RONS of cold plasma were responsible for Pseudomonas fluorescens inactivation and related to activation of intracellular antioxidant defense system and regulation of genes expression related to amino acid metabolism and energy metabolism, which promoting cellular process, catalytic activity and other biochemical pathways.
Assuntos
Gases em Plasma , Pseudomonas fluorescens , Espécies Reativas de Oxigênio , Pseudomonas fluorescens/metabolismo , Gases em Plasma/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Espécies Reativas de Nitrogênio/metabolismo , Microbiologia da Água , Viabilidade Microbiana/efeitos dos fármacosRESUMO
Selective generation of sufficient pyroptosis inducers at the tumor site without external stimulation holds immense significance for a longer duration of immunotherapy. Here, we report a cascade-amplified pyroptosis inducer CSCCPT/SNAP that utilizes reactive nitrogen species (RNS), self-supplied from the diffusion-controlled reaction between reactive oxygen species (ROS) and nitric oxide (NO) to potentiate pyroptosis and immunotherapy, while both endogenous mitochondrial ROS stimulated by released camptothecin and released NO initiate pyroptosis. Mechanistically, cascade amplification of the antitumor immune response is prompted by the cooperation of ROS and NO and enhanced by RNS with a long lifetime, which could be used as a pyroptosis trigger to effectively compensate for the inherent drawbacks of ROS, resulting in long-lasting pyroptosis for favoring immunotherapy. Tumor growth is efficiently inhibited in mouse melanoma tumors through the facilitation of reactive oxygen/nitrogen species (RONS)-NO synergy. In summary, our therapeutic approach utilizes supramolecular engineering and nanotechnology to integrate ROS producers and NO donors of tumor-specific stimulus responses into a system that guarantees synchronous generation of these two reactive species to elicit pyroptosis-evoked immune response, while using self-supplied RNS as a pyroptosis amplifier. RONS-NO synergy achieves enhanced and sustained pyroptosis and antitumor immune responses for robust cancer immunotherapy.
Assuntos
Imunoterapia , Estresse Oxidativo , Piroptose , Espécies Reativas de Nitrogênio , Microambiente Tumoral , Piroptose/efeitos dos fármacos , Animais , Espécies Reativas de Nitrogênio/metabolismo , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Espécies Reativas de Oxigênio/metabolismo , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/química , Melanoma Experimental/terapia , Melanoma Experimental/imunologia , Melanoma Experimental/patologiaRESUMO
Reactive oxygen species (ROS), reactive sulfur species (RSS), metal ions, and nitrogen species (RNS) play important roles in a variety of biological processes, such as a signal transduction, inflammation, and neurodegenerative damage. These species, while essential for certain functions, can also induce stress-related diseases. The interrelation between ROS, RSS, Metal ions and RNS underscores the importance of quantifying their concentrations in live cells, tissues, and organisms. The review emphasizes the use of small-molecule-based fluorescent/chemodosimeter probes to effectively measure and map the species' distribution with high temporal and spatial precision, paying particular attention to in vitro and in vivo environments. These probes are recognized as valuable tools contributing to breakthroughs in modern redox biology. The review specifically addresses the relationship of HOCl/ClOâ¾ (hypochlorous acid/Hypochlorite) with other reactive species. (Dual sensing probes).
Assuntos
Corantes Fluorescentes , Ácido Hipocloroso , Espécies Reativas de Oxigênio , Ácido Hipocloroso/análise , Ácido Hipocloroso/química , Corantes Fluorescentes/química , Humanos , Animais , Espécies Reativas de Oxigênio/metabolismo , Espécies Reativas de Oxigênio/análise , Espécies Reativas de Nitrogênio/análise , Espécies Reativas de Nitrogênio/química , Espécies Reativas de Nitrogênio/metabolismoRESUMO
The rapid perfusion of cerebral arteries leads to a significant increase in intracranial blood volume, exposing patients with traumatic brain injury to the risk of diffuse brain swelling or malignant brain herniation during decompressive craniectomy. The microcirculation and venous system are also involved in this process, but the precise mechanisms remain unclear. A physiological model of extremely high intracranial pressure was created in rats. This development triggered the TNF-α/NF-κB/iNOS axis in microglia, and released many inflammatory factors and reactive oxygen species/reactive nitrogen species, generating an excessive amount of peroxynitrite. Subsequently, the capillary wall cells especially pericytes exhibited severe degeneration and injury, the blood-brain barrier was disrupted, and a large number of blood cells were deposited within the microcirculation, resulting in a significant delay in the recovery of the microcirculation and venous blood flow compared to arterial flow, and this still persisted after decompressive craniectomy. Infliximab is a monoclonal antibody bound to TNF-α that effectively reduces the activity of TNF-α/NF-κB/iNOS axis. Treatment with Infliximab resulted in downregulation of inflammatory and oxidative-nitrative stress related factors, attenuation of capillary wall cells injury, and relative reduction of capillary hemostasis. These improved the delay in recovery of microcirculation and venous blood flow.